Many factors including neural, hormonal, myogenic, oxygen, metabolic and flow-dependent contribute to local vascular resistance and hence to local microvascular blood flow regulation. The long-term goals of this study are to determine the contribution of the endothelium of arterioles to hormonal, myogenic, oxygen and flow-dependent regulation of blood flow in red and white skeletal muscles. By comparing these regulatory modalities in red and white skeletal muscle, we will be able to determine if there are differences in these mechanisms in these tissues that could account for the differences observed in resting blood flow and local microvascular responses. To accomplish these goals, studies will be performed on isolated cannulated and pressurized arterioles, of different sizes, from rat cremaster, soleus, extensor digitorum longus and gracilis skeletal muscle in a myograph chamber, under conditions of no-flow or flow. Preliminary studies have demonstrated the feasibility of all aspects of the study. Depending on the individual protocol, arteriolar diameter, pressure, and flow will be measured and recorded as well as bath temperature, pH and oxygen tension. Arteriolar responses to endothelium-dependent and independent vasoactive substances (hormonal), changes in transmural pressure (myogenic response), changes in bath oxygen tensions (oxygen), and shear-stress (flow-dependent) will be determined in vessels before and after removal of the endothelium in order to determine the role of the endothelium in these important microvascular responses. As it is now well known that the endothelium produces a number of important vasoactive substances that can be released under certain conditions, experiments will also be performed in the presence and absence of either indomethacin or N-G-nitro-L-arginine, in order to assess the role and relative importance of prostaglandins and EDRF in the responses. These studies will provide new and important information that could potentially explain the basis for the differences in resting blood flow, blood flow regulation and blood flow responses in different types of skeletal muscles.